tbuckley/cabot-search huggingface dataset:
QOL-13. Impact of hearing loss on neuropsychological functioning in children treated for medulloblastoma: A report from the Children’s Oncology Group (COG)
Authors: Leanne Embry, Kristina Hardy, Etan Orgel, Yu Wang, Jeff Michalski, Yimei Li, Patricia Cullen, Paul Colte, Johnnie Bass
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND/OBJECTIVE: We prospectively examined neuropsychological outcomes and ototoxicity in children with average-risk medulloblastoma. METHODS: Eligible patients included those treated on COG protocol ACNS0331 who completed audiograms at end of therapy or one-year off-therapy, and neuropsychological assessments between 2- and 5-years post-diagnosis. Conventional pure-tone audiometric evaluations (0.25-8kHz) were assigned an ototoxicity grade based on the International Society of Pediatric Oncology (SIOP) grading scale. Grade for the better hearing ear was used for analyses. Participants were divided into two groups: SIOP grade≥3 hearing loss (HL) versus SIOP grade&amp;lt;3. Cutoff score of 60 on BASC-2 was used to dichotomize parent-reported anxiety and depression scores as ‘low’ or ‘high’. RESULTS: Data were available for 113 children (66% male; 86% white), aged 3.0-18.5 at diagnosis (Mean=9.1). One-quarter (24.8%, n=28) had at least moderate HL (≥ SIOP grade 2), and 12.3% (n=14) had severe HL (≥ SIOP grade 3). After controlling for radiation exposure and age, children with severe HL showed significantly higher levels of anxiety (OR=5.9, 95%CI 1.3-26.0, p=0.0195) and borderline differences in depression (OR=4.0, 95%CI 1.0-16.5, p=0.0563), but no differences in cognitive functioning when compared to other participants. When moderate and severe HL were combined in exploratory analyses, significantly greater anxiety (OR=9.0, 95%CI 2.1-37.4, p=.0027) and depression (OR=4.6, 95%CI 1.3-15.7, p=.0165) were observed. CONCLUSIONS: Survivors of pediatric medulloblastoma with moderate to severe HL evidenced greater psychosocial, but not neurocognitive, difficulties compared to those with no or mild HL. It may be that modern treatment protocols generally preserve cognitive functioning such that associations between HL and cognitive impairment are no longer significant. It is also possible that neurocognitive risk associated with HL may not manifest until survivors are further from diagnosis. In contrast, survivors with HL may be at greater risk for negative psychosocial adjustment, suggesting that increased monitoring of mental health outcomes is warranted.
Two years of the Australian Rare Cancer Portal: a national referral service for rare cancer information and research.
Authors: Chloe L. Georgiou, Damien Kee, Lia Papadopoulos, Reece Caldwell, Allison Bourne, Javier Haurat, Maureen Turner, David Goldstein, Clare L. Scott
Journal: Journal of Clinical Oncology (2022)

e18581 Background: Rare cancers (RC) occur at incidence &lt; 6/100,000 and accessing treatment and evidence-based care can be challenging. Australia’s geographical distance adds complexity when referring to RC sub-specialists, clinical trials or research. The Australian Rare Cancer (ARC) Portal aims to address this unmet need. Methods: The ARC Portal is a free online academic referral hub designed to facilitate rare cancer clinical care and research. Registered cancer specialists can request RC guidelines, expert advice and molecular testing/interpretation. Patient consent allows researchers access to de-identified clinical data, with optional consent for biospecimen access, for dedicated rare cancer research projects (Melbourne Health HREC/15/MH/396). Portal case reports are collated by research fellows with reference to published evidence and expert opinion to inform treating clinician decision making. Surveys are sent at 3 time points following case completion to assess the ARC Portal impact on patient management. The ARC Portal is funded by Omico, with support from BioGrid Australia, Rare Cancers Australia and the Stafford Fox Rare Cancer Program. Results: Over two years, 924 patients have been enrolled into the ARC Portal. Demographics include 73% females, 27% males, at different disease stages from initial diagnosis (23%), on relapse/ progression (48%) or with stable disease/in remission (29%). The spread of incidence of individual cancers varied from 6/100,000 to &lt; 0.1/100,000. Primary tumour types include gynaecological (44.4%), gastrointestinal (19%), thoracic (6%), ocular (5.2%), soft tissue (3.8%), breast (3.6%), skin (3.0%), and CNS tumors (2.5%). Endocrine, head and neck, urological, and cancers of unknown primary comprised the remaining 12.5% of cases. Longer term follow up of 100 cases demonstrated ARC Portal reports impacted clinician decision making in at least 42%. This included subsequent lines of treatment, molecular testing access or clinical trial enrolment. Conclusions: The ARC Portal uses an online centralized streamlined approach to overcome challenges and inequities inherent in rare cancer care, by optimizing clinician access to RC expertise and clinical trials; and to facilitate future RC discoveries by enabling research through collection of clinical data and accessible annotated biospecimens.
Impact of germline mutations on surgical decision-making in women with DCIS.
Authors: Rachel E Ellsworth, Lauren Turza, Leann A Lovejoy, Clesson E Turner, Craig D Shriver
Journal: Journal of Clinical Oncology (2022)

10576 Background: Ductal carcinoma in situ (DCIS) is both a malignant, yet pre-invasive disease of the breast. While the majority of DCIS have a low risk of recurrence, a subset of women with germline pathogenic variants (PV) in cancer predisposition genes are at increased risk for breast cancer recurrence. Uptake of genetic testing and treatment with risk-reducing surgeries (RRS), including bilateral mastectomy (BM), in women with DCIS, has not been well-studied. The aim of this study was to determine the prevalence of PVs in women with DCIS and the impact on surgical decision making. Methods: All women diagnosed with unilateral DCIS 2001-2020 enrolled in the Clinical Breast Care Project were identified. Demographic, genetic test results and surgical procedures were extracted from the database. Test-eligibility was assigned using National Comprehensive Cancer Network (NCCN) criteria. Panel genetic testing was performed in the research setting using DNA from 465 women. Statistical analyses were performed using Fisher’s exact tests and Chi-square analyses with p &lt; 0.05 defining significance. Results: The overall PV frequency in women with DCIS was 8.1%. Within the test-eligible group, 35.1% pursued clinical genetic testing, including 13.2% who pursued testing only after a second cancer event. Of the 39 women with PV, 20 (51.3%) were detected only in the research setting, with 11 (28.2%) of these women not eligible for genetic testing based on NCCN criteria. In the 419 women who did not undergo BM at diagnosis, recurrence was significantly higher (p = 0.001) in women with PV (33.3%) compared to those without PV (11.6%). Conclusions: Genetic testing is suboptimal in women with a primary diagnosis of DCIS. Twenty percent of women with PV, who may have benefited from BM, did not undergo genetic testing at the time of diagnosis and recurred. These data suggest that genetic testing at the time of diagnosis should be standard for all women with DCIS.
RARE-22 Characterizing the landscape of structural variants in adamantinomatous craniopharyngioma
Authors: Danny Jomaa, Prasidda Khadka, Dana Novikov, Alexandra L Condurat, Jessica W Tsai, Frank Dubois, Shu Zhang, Kevin Zhou, Rose Gold, Cecilia Sousa, Jayne Vogelzang, Eric Prince, Sophie Lu, Veronika Slivova, Georg W Otto, Sergi Castellano Hereza, David Ashley, Aaron A Cohen-Gadol, Eric Thompson, Rameen Beroukhim, John Apps, Juan Pedro Martinez-Barbera, Todd Hankinson, Pratiti Bandopadhayay
Journal: Neuro-Oncology (2022)

Abstract INTRODUCTION: Adamantinomatous craniopharyngiomas (ACPs) are rare brain tumors that primarily occur in children and impact long-term morbidity and mortality. The canonical driver mutation for ACP growth occurs in CTNNB1 and leads to constitutive activation of the Wnt/β-catenin signaling pathway. In this study, we outline the genomic, transcriptomic, and structural variant (SV) landscape in a cohort of 41 ACP samples. METHODS: We performed whole-genome sequencing (WGS) and RNA-sequencing of 41 ACP samples. Matched normal samples were also characterized by WGS. Mutect2 was used to detect single nucleotide variants (SNVs) and indels, and copy number data was generated using the GATK pipeline. SvABA was used to perform SV analysis and to identify significantly recurrent breakpoints and juxtapositions. DESeq2 was used to perform differential gene expression analysis based on clinical and molecular annotation data. RESULTS: 29/41 (70%) of the ACP samples harbored missense mutations in exon 3 of CTNNB1, all of which have previously been reported in ACP tumors. SV analysis identified a median of 11.5 events per tumor. Overall, 9.7% of events were interchromosomal. Of the remainder, the majority (78.6%) were deletions. No SVs occurred within CTNNB1. A positive correlation (r = 0.533) was observed between the frequency of SVs and SNVs within samples. Analysis of significantly recurring breakpoints (SRBs) did not identify recurrent breakpoint events. Differential gene expression analysis comparing samples with and without CTNNB1 variants identified 2,143 differentially expressed genes with q-value &amp;lt; 0.05. CONCLUSION: This study identifies activating mutations in exon 3 of CTNNB1 in a large cohort of ACP samples. We also integrate SV and transcriptomic data to comprehensively investigate ACP tumor genomes and identify putative novel tumorigenic mechanisms that advance our understanding of ACP biology.
Peri-operative outcomes of open versus robot-assisted simple prostatectomy: Results from two high-volume centres
Authors: S. Scarcella, A. Mottaran, C.A. Bravi, J. Van Der Jeugt, P. Piazza, L. Sarchi, M. Paciotti, S. Puliatti, P. Umari, C. Giuloni, G. Milanese, L. Dell'Atti, D. Castellani, A. Galosi, R. De Groote, P. Schatteman, A. Mottrie
Journal: European Urology (2022)
PATH-05 Challenge and clinical relevance of a non-matching classifier output in genome-wide DNA methylation analysis for CNS neoplasms in pediatric and adolescent patients
Authors: Richard Drexler, Alicia Eckhardt, Helena Bode, Katrin Lamszus, Manfred Westphal, Ulrich Schüller, Malte Mohme
Journal: Neuro-Oncology (2022)

Abstract OBJECTIVE: The molecular classification of CNS tumors has revolutionized our understanding of the biological heterogeneity and diversity of tumor subtypes. DNA methylation-based classification allows to discriminate subtypes. Although DNA methylation-based classification can diagnose tumors with high specificity, there are tumors which cannot be classified. We aimed to gain further insight into these challenging cases. METHODS: Overall, 21 patients with a CNS tumor that was non-classifiable (confidence score &amp;lt;0.3), or had a low confidence score (&amp;lt;0.9) using the DNA methylation-based classifier version 11b4, were included. Tumors were re-classified using version (v12.3), and clinical data were analyzed. RESULTS: A total of 21 pediatric and adolescent brain tumors with a calibrated score below 0.9 in the classifier output were identified. Of these, 11 patients (52.4 %) were assigned to the “no matching methylation class” with a score below 0.3. IDH-wild type glioblastoma (23.8 %), ETMR (14.3 %), and DMG (14.3 %) were the most common histological diagnoses. Surgical and clinicopathological features as well as DNA input and tumor purity did not influence the confidence score. Cases with non-classifiable tumors had a significantly longer time until a decision for adjuvant therapy (p&amp;lt;0.01). Application of the latest classifier version v12.3 led to a re-classification of 9 (42.9 %) cases, of which 5 cases (55.6 %) had an improved calibrated score. CONCLUSION: Our study presents unclassifiable cases and the possible clinical impact when waiting for the accurate diagnosis in these challenging cases. Even though DNA methylation profiling significantly contributes to advanced CNS tumor diagnostics, clinicians should be aware of a prolonged interval to treatment initiation, especially for highly malignant brain tumors. Therefore, we would recommend to schedule adjuvant treatment as early as possible, if surgical and histological results are suspicious for this disease.
The role of 3-D imaging reconstruction in real-life urologic practice: Results from a global survey
Authors: M.C. Sighinolfi, A. Dourado, S. Assumma, A. Cassani, F. Annino, V. Patel, F. Annino, V. Patel, M. Moschovas, G. Cacciamani, G. Bozzini, A. Gregori, E. Morini, J. Simoes, A. Eissa, S. Puliatti, L. Sarchi, S. Micali, B. Rocco
Journal: European Urology (2022)
Urinary and sexual outcomes after water vapour intraprostatic injection (Rezum procedure): Results from prospective multicentric Italian study
Authors: D. Campobasso, G. Siena, P. Chiodini, E. Conti, F. Franzoso, D. Maruzzi, E. Martinelli, F. Varvello, C. De Nunzio, R. Autorino, G. Ferrari, L. Cindolo
Journal: European Urology (2022)
Urolithiasis in patients with kidney transplantation: Multicenter KSER research series
Authors: K.H. Shim, K. Choi, W.B. Kim, S.W. Yang, D.K. Kim, M.S. Choo, D.Y. Chung, H.D. Jung, S.W. Lee, S. Paick, S.H. Jeon, J.Y. Lee
Journal: European Urology (2022)
MODL-29. Molecular Landscape of a comprehensive panel of pediatric brain cancer Patient-derived orthotopic xenograft (PDOX) models inform unique targets for drug responsiveness
Authors: Frank K Braun, Sebastian Brabetz, Lin Qi, Yuchen Du, Mari Kogiso, Hui Yuan Zhang, Holly Linday, Wanyee Teo, Patricia Baxter, Jack M F Su, Adesina Adekunle, Bae Goeun, Reid T Powell, Donald W Parsons, Murali Chintagumpala, Clifford C Stephan, Stefan Pfister, Ching C Lau, Marcel Kool, Xiao-Nan Li
Journal: Neuro-Oncology (2022)

Abstract Brain tumor is a leading cause of cancer related death in children. In addition to replicating histopathology, animal models faithfully replicating genetic/epigenetic abnormalities, molecular subtypes and broad inter-tumoral heterogeneities are needed. Through direct implantation of patient surgical or autopsied tumor tissues into matching locations in the brains of SCID mice, we developed a panel of 150 PDOX mouse models. Here, we report the analysis of 74 of the 150 PDOX models, 45 matching patient tissues and 60 non-tumorigenic samples to a well-annotated reference cohort of 2,801 methylation profiles of primary brain tumors. Our data showed that the lack of tumorigenicity was neither correlated with molecular subtypes nor predicted by low cell viabilities of the patient samples. Methylation profiling identified PDOX models representing nearly a full spectrum of molecular subtypes of pediatric brain tumors including GBM, medulloblastoma, ependymoma and ATRT. Direct comparison with the original patient tumors confirmed the replication of molecular subtypes. ONCOplot [FB1] analysis of PDOX models derived from matching pairs of primary and recurrent tumors (n=8) revealed close clustering with the patient tumors. Investigation of metastatic properties was performed in 13 MB models by harvesting and sub-transplanting matching PDOX primary tumors in the cerebella and metastatic tumors in the spinal cords. To confirm the potential and power of PDOX models in preclinical drug testing, we applied fractionated radiation (2 Gy/day x 5 days) and optimized multi-agent combinatory chemotherapies in MB models of the four major subgroups. High-throughput combination drug screening with ~ 8,000 drugs in PDOX-derived GBM cell lines and primary cultures of MB PDOX cells identified a library of ~ 3,500 drugs that were active in pediatric brain tumors. In summary, this study provides detailed information on molecular subclassification of a uniquely large cohort of PDOX models to serve as essential tools for brain tumor research.
Transcriptomic profiling of upper tract urothelial carcinoma: Utility of the consensus molecular classification of bladder cancer, differential immune signatures and molecular heterogeneity
Authors: J. Fontugne, E. Xylinas, C. Krucker, V. Dixon, C.S. Groeneveld, H. Pinar, G. Califano, M. Bucau, J. Verine, F. Desgrandchamps, J.F. Hermieu, F. Radvanyi, Y. Allory, A. Masson-Lecomte
Journal: European Urology (2022)
HGG-32. Durable response to mTOR inhibitor after failing Checkpoint inhibitors in Ultra-Hypermutated High grade glioma in context of CMMRD
Authors: Kriti Hegde, Christine Dahl, Sarita Depani, Darren Hargrave, Minou Oostveen, Fernando Aguirregomezcorta, Owase Jeelani, Kristian Aquilina, Jenny Gains, Yen Ching, Thomas Jacues, Ashirwad Merve, Jane Chalker, Dilys Addy, Saira W Ahmed, Shireen Yasin, Kshitij Mankad, Olivia Carney, Sniya Sudhakar, Felice D'Arco, Ulrike Loebel, Mette Jorgensen
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND: Paediatric High Grade Gliomas (HGG) have poor outcomes with conventional treatment. HGG in association with constitutional DNA mismatch repair deficiency (CMMRD) are hypermutated and have shown dramatic response to checkpoint inhibitors. Salvage following progression or failure to respond to check point inhibitors has rarely been reported. We describe a successful alternative therapeutic approach targeting the activated pathway (mTOR) in a hypermutated HGG. CASE SUMMARY: A 6-year-old girl presenting with seizures was diagnosed with left frontal lobe HGG with concurrent neck mass (Pilomatrixoma). Presence of synchronous tumours raised the possibility of cancer predisposition; the HGG was hypermutated with germline PMS2 mutation confirming diagnosis of CMMRD. Near total resection was undertaken followed by focal radiotherapy 54 Gy, with 1 cycle of concomitant CCNU. MRI post radiotherapy showed tumour progression. Anti-PDl inhibitor Nivolumab was commenced. CTLA-4 antibody, Ipilimumab was added after 4 cycles of Nivolumab due to poor response. Tumour response was seen, but dual therapy had to be discontinued due to toxicity. The tumour progressed following further single agent Nivolumab. In view of multiple mutations in the mTOR pathway (NF1, PIK3/PTEN, TSC1, TSC2), a mTOR inhibitor, Everolimus was commenced. There was 25% tumour reduction after 4 weeks treatment and further reduction after 6 months. Resection of residual tumour showed necrotic tissue only. There continues to be a sustained response to Everolimus for over 12 months. DISCUSSION: Approximately a third of CMMRD HGG respond to checkpoint inhibitors. For those that don’t, these hypermutated tumours offers the possibility of targeting specific molecular pathways. Response to Everolimus in HGG harbouring mTOR aberrations have been described. To our knowledge this is the first report of successful use of mTOR inhibitor in CMMRD HGG. CONCLUSION: Targeted molecular treatment for patients with CMMRD hypermutated brain tumours should be considered according to the mutated pathways.
Digital single-operator pancreatoscopy for the treatment of symptomatic pancreatic duct stones: a prospective multicenter cohort trial
Authors: Christian Gerges, David Albers, Lukas Schmitz, Elisabetta Goni, Annalisa Cappello, Jörg Schirra, Markus Casper, Arno J. Dormann, Dirk Hartmann, Marcus Hollenbach, Markus Schneider, Ulrike W. Denzer, Alexander Dechene, Markus Dollhopf, Julia Mayerle, Brigitte Schumacher, Erwin-Jan M. van Geenen, Horst Neuhaus, Peter D. Siersema, Mark Ellrichmann, Torsten Beyna
Journal: Endoscopy (2022)

Digital single-operator pancreatoscopy (DSOP)-guided lithotripsy is a novel treatment modality for pancreatic endotherapy, with demonstrated technical success in retrospective series of between 88 % and 100 %. The aim of this prospective multicenter trial was to systematically evaluate DSOP in patients with chronic pancreatitis and symptomatic pancreatic duct stones.Patients with symptomatic chronic pancreatitis and three or fewer stones ≥ 5mm in the main pancreatic duct (MPD) of the pancreatic head or body were included. The primary end point was complete stone clearance (CSC) in three or fewer treatment sessions with DSOP. Current guidelines recommend extracorporeal shock wave lithotripsy (ESWL) for MPD stones > 5 mm. A performance goal was developed to show that the CSC rate of MPD stones using DSOP was above what has been previously reported for ESWL. Secondary end points were pain relief measured with the Izbicki pain score (IPS), number of interventions, and serious adverse events (SAEs).40 chronic pancreatitis patients were included. CSC was achieved in 90 % of patients (36/40) on intention-to-treat analysis, after a mean (SD) of 1.36 (0.64) interventions (53 procedures in total). The mean (SD) baseline IPS decreased from 55.3 (46.2) to 10.9 (18.3). Overall pain relief was achieved in 82.4 % (28/34) after 6 months of follow-up, with complete pain relief in 61.8 % (21/34) and partial pain relief in 20.6 % (7/34). SAEs occurred in 12.5 % of patients (5/40), with all treated conservatively.DSOP-guided endotherapy is effective and safe for the treatment of symptomatic MPD stones in highly selected patients with chronic pancreatitis. It significantly reduces pain and could be considered as an alternative to standard ERCP techniques for MPD stone treatment in these patients.
Patient-Relevant Outcomes in Psoriasis
Authors: Niels Hilhorst, Elfie Deprez, Nele Pauwels, Lynda Grine, Jo Lambert, Isabelle Hoorens
Journal: JAMA Dermatology (2022)

There is a need to define which outcomes matter to patients with psoriasis to deliver value for the patient when managing their condition.To generate a comprehensive overview of all outcomes relevant in the management of psoriasis as defined by patients.A systematic review was performed by searching 3 databases (MEDLINE, Embase, and Web of Science) from August 1, 2019, until March 27, 2021, using a comprehensive search strategy consisting of 4 concepts including psoriasis, patients, outcomes, and relevance. A (citing) reference search was also performed of all retrieved articles. Two independent reviewers screened the retrieved records by title/abstract against the eligibility criteria. Studies were eligible for inclusion if they reported on the importance of outcomes for patients with psoriasis. No language restrictions were used. Data extraction and quality assessment were also performed independently. Quality assessment was done using the QUALSYST tool.In total, 10 365 records were screened for eligibility, of which 24 studies were included for synthesis. A total of 23 317 patients were evaluated, and 273 (154 unique) items were retrieved. These items were aggregated into 23 outcomes: (almost) complete clearance; symptom control; difficult location clearance; time to clearance; treatment efficacy, sustainability, safety, tolerability, and convenience; comorbidity control; daily and social activity; emotional well-being; intimate relationships; productivity; health-related quality of life; confidence in care; control of disease; communication with care professional; information from other sources than care professional; and cost of care (societal and for the patient). These were then further grouped into 4 core areas: physical/clinical, life impact, resource use, and adverse effects. The mean overall quality of the studies was 75.6% (range, 35.7%-100%).This systematic review analyzed patient-relevant outcomes reported in patients with psoriasis to aid in the transition to a value-based treatment approach.